Pathogen inactivation methods to prevent transfusion-transmissible arboviruses: A systematic review and meta-analysis

Abstract

Objective: Arboviruses are emerging as a relevant threat to transfusion safety. Pathogen inactivation methods (PIMs) may reduce the risk of transmission through transfusion, as long as they meet minimum standards for effectiveness. This study aims to assess the log reduction of viral load achieved with different PIMs, according to the blood product they are used on and the arbovirus targeted.

Methods: Systematic literature review and meta-analysis. Searches were conducted in MEDLINE and Embase. The study protocol was registered in PROSPERO CRD42022312061. We selected records reporting the log reduction of viral load achieved with the main PIMs (amotosalen + UVA light [INTERCEPT], riboflavin + UV light [Mirasol], methylene blue + visible light/UVC light [THERAFLEX], solvent detergent, amustaline [INTERCEPT] and PEN110 [Inactine]), applied to any blood product (plasma, platelets, red blood cells or whole blood) and for any arbovirus. The log reduction of viral loads was assessed by obtaining the mean log reduction factor (LRF). We compared and classified the LRF of different techniques using statistical methods.

Results: We included 59 publications reporting LRF results in 17 arboviruses. For 13 arboviruses, including Chikungunya virus, Dengue virus, West Nile virus and Zika virus, at least one of the methods achieves adequate or optimal log reduction of viral load-mean LRF ≥4. The LRF achieved with riboflavin + UV light is inferior to the rest of the techniques, both overall and specifically for plasma, platelets preserved in platelet additive solution (PAS)/plasma, and red blood cells/whole blood. The LRF achieved using Mirasol is also lower for inactivating Chikungunya virus, Dengue virus and Zika virus. For West Nile virus, we found no significant differences. In plasma, the method that achieves the highest LRF is solvent/detergent; in platelets, THERAFLEX and INTERCEPT; and in red blood cells/whole blood, PEN110 (Inactine).

Conclusion: Not all PIMs achieve the same LRF, nor is this equivalent between the different arboviruses or blood products. Overall, the LRFs achieved using riboflavin + UV light (Mirasol) are inferior to those achieved with the rest of the PIMs. Regarding the others, LRFs vary by arbovirus and blood product. In light of the threat of different arboviruses, blood establishments should have already validated PIMs and be logistically prepared to implement these techniques quickly.

Keywords: Chikungunya virus; Dengue virus; West Nile virus; Zika virus; arboviruses; blood donors; blood safety; blood transfusion; virus inactivation.